An analytical system usually comprises a separation system and an analysis system. The separation system and an analysis system are usually separated in time and space. A frequently encountered problem is that there is a loss of sample components in one of the systems or in the interface in between the systems.
Most of the analytical methods currently in use in chemical analysis are not completely selective. Because of this, there is a need for separation of the sample components prior to their presentation for the analytical system. At present date the most frequently used separation systems are based on chromatography. The first separation utilizing chromatography was reported by Tswett in 19031. When allowing a plant extract to flow through a column packed with calcium carbonate, the plant pigments where separated in colored bands. The appearance of these colored bands founded the name for the technique, i.e. chromatography (from Greek chromos=color, and grafe=to write). There are some features that are in common for all types of chromatography. A sample is diluted, and transported, in a mobile phase, which can be a liquid, a gas or a supercritical fluid. The mobile phase passes a stationary phase that is immiscible with the mobile phase. The stationary phase is either fixed in a column or bond to a surface. These two phases, i.e. the mobile and the stationary phase, are chosen in a way that allows the sample components to be distributed between them. Different types of sample components will distribute themselves somewhat differently between the phases. Sample components primarily present in the mobile phase will quickly follow this phase through the column. Other components that are staying in the stationary phase for a longer time will also stay a longer time in the column. This difference between different sample components yields a mobility difference, allowing the sample components to be separated from each other. Different types of chromatographic systems arise as a consequence of the different types of mobile and stationary phases that are possible to use.
1Tswett, M. S.; Protok, T.; Varshav Obsch. Estestvoispyt Otd. Biol. 14 (1905). 
Liquid chromatography (LC) is characterized by a liquid mobile phase. The stationary phase can be either a liquid adsorbed to a solid material, organic molecules bond to solid surface, a solid material, an ion-exchange material or a solid material with interconnected pores. In the porous packing material the sample components are distributed according to their sizes. One advantage with this type of chromatography is that it is compatible with most types of analytical systems that do not destroy the analytes. Furthermore, the LC type of chromatography can be open and handle large quantities of sample for preparative applications.
Gas chromatography (GC) is characterized by a gaseous mobile phase. The stationary phase can be a liquid that is adsorbed to a surface, organic molecules bond to a surface or a solid material. One drawback of this system is that the analytical system used mostly destroys the sample components. An analytical system frequently used in combination with GC is flame ionization detection (FID). Non-volatile compounds can not be analysed with this system and the system must also be closed.
Supercritical fluid chromatography (SFC) is a hybrid of LC and GC. A supercritical fluid has physical properties in-between those of a gas and a liquid. Sample components that are not volatile and does not have chemical groups that enables them to be detected by analytical systems compatible with LC (mass spectrometry excluded) comprises the major part of SFC analyses. A solid material with organic molecules bond to it is most frequently applied as stationary phase.
Capillary electrophoresis (CE) originates from electrophoresis that was developed by Tiselius in 1937 for analysis of bio-macromolecules2. The basis of electrophoresis is the mobility of a charged component in a solution over which an electric field has been applied. The mobility of the component is related to its charge state and its friction against the surrounding media. The frictional force is related to the size of the compound, i.e. the hydrodynamic radius. A current evolves as charged species starts to migrate in an electric field and thus heat is emitted. In order to reduce the magnitude of the generated heat, CE was invented3,4 to allow efficient heat emission from the separation media. A flat flow velocity profile is obtained in CE due to the formation of an electrical double layer at the inner walls of the capillary. This flat flow velocity profile allow the analytes to be forced unselectively through the capillary with a velocity independent of where in the cross-section of the capillary the analyte is situated. The obtained separation efficiency is therefore considerably higher than that obtained in LC, and then especially for bio-macromolecules which have very low diffusion coefficients5.
2Tiselius, A. Trans. Faraday Soc. 1937, 33, 524. 
3Hjertén, S., Chromatogr, Rev. 1967, 9, 122. 
4Virtanen, R. Acta Polytechnica Scand. 1974, 123, 1. 
5Monnig, C. A. and Kennedy, R. T. Anal. Chem. 1994, 66, 280R. 
Micellar electro kinetic chromatography (MEKC) utilizes the distribution of sample components between the mobile phase (electrolyte) and micelles in the electrolyte6. The system is useful for separation of sample components with the same electrophoretic mobility but with different affinities for the micelles. MEKC has primarily been applied to separations of neutral sample components, sample components having the same mass to charge ratio and chiral sample components7.
6Terabe, S. T., Otsuka, K., and Ando, T., Anal. Chem. 1985, 57, 834. 
7Mazzeo, J. R., Micellar electrokinetic chromatography, Handbook of Capillary Electrophoresis 2nd ed. 1997, CRC Press, Inc. 
Capillary electrochromatography (CEC) is a hybrid between CE and LC. A major difference between CE and LC is that the sample is transported through the separation system in a flat flow velocity profile, compared to the parabolic flow velocity profile found in LC. The separation mechanism is a combination of the electrophoretic mobilities of the sample components and the different distributions of the sample components between the electrolyte and the stationary phase. The stationary phase can either be particle based, packed inside the capillary, or monolithic, i.e. a continuous stationary phase with interconnected pores. It has been shown both theoretically8 and experimentally9 that the separation efficiency in CEC is superior to that in LC.
8Knox, J. H. and Grant, I. H., Chromatographia 1987, 24, 135, 1987. 
9, J. H. and Grant, I. H., Chromatographia 1991, 32, 317. 
Separations have also been performed utilizing a mobile solid phase in a partial filling application10,11 of CEC (FIG. 1.). Molecularly imprinted polymer (MIP) nanoparticles have been used to perform highly efficient enantiomer separations of chiral sample components utilizing partial filling CEC with UV-detection12. The primary benefit of the partial filling technique is that a mobile solid phase can be used without hampering the analysis system. The mobile solid phase is suspended in the electrolyte and injected as a plug with a certain length prior to the sample. The separation system is designed (length of plug and length of capillary) so that the sample has time to migrate through the particle plug and reach the detection window prior to the light scattering and light absorbing particle plug. The drawbacks of the partial filling technique are related to the difficulties associated with the adjustment of the migration velocities of the sample components and the mobile solid phase particle plug. The system must be designed to enable the sample components to pass the particle plug and reach the detection window prior to the particle plug.
10L. Valtcheva, J. Mohammad, G. Pettersson, S. Hjertén J. Chromatogr. 1993, 638, 263-267. 
11A. Amini, U. Paulsen-Sorman, D. Westerlund, Chromatographia 1999, 36, 35. 
12Schweitz, L., Spégel P., Nilsson, S. Analyst 2000, 125, 1899-1901. 
In common for all above mentioned separation systems is that the solid phase (i.e. the stationary phase or the mobile solid phase) is not directly compatible with the analysis system. The separation system thus suffers from irreversible adsorption of sample components onto the solid phase that will never reach the analysis system. These sample components will thus never be detected and determined. The analysis system is most often situated at the outlet of the separation system, imaging detection devices excluded13.
13Method and detection for separation processes, PCT/SE93/00305 
Mass spectrometers (MSs) are analysis systems that analyzes charged (ionic) sample components. The creation of gaseous ions from charged droplets is referred to as electro spray ionization (ESI). ESI was suggested as an ionization source for MS in the early 1960's by Dole et al. 14 Today ESI is one of the most common ionization sources for MS. Dole proposed a mechanism for ESI that was called the charged residual model (CRM). CRM (FIG. 2.) describes the fast size reduction of a small (nanometer to micrometer) charged droplet accelerated in an electric field. The size reduction is due to solvent evaporation, which proceeds until the Rayleigh limit of the droplet is reached, i.e. the limit where the repulsive forces between charges on the surface of the droplet are larger than the surface tension keeping the droplet together. As this limit is passed the droplet explodes, causing the formation of several smaller droplets. In the end, following several repetitions of evaporations and explosions, respectively, a single droplet only contains one or two sample components. Charges present in the droplet will be transferred to the sample components during CRM. In 1979 Irbane et al presented a similar model for the creation of gaseous ions15.
14Dole, M.; Mach, L. L.; Hines, R. L.; Mobley, R. C.; Ferguson, L. P.; Alice, M. B. J. Chem. Phys. 1968, 49, 2240. 
15Thomson, B. A.; Irbane, J. V. J. Chem. Phys. 1979, 71, 4451. 
In the middle of the 1980's, Fenn et al demonstrated a functional ES-MS16. The combination of ESI and MS requires that charged droplets can be created from the sample component solution. This can be achieved by allowing the sample to be pumped through a flow column, most often a capillary, while applying a potential difference (voltage) between the capillary outlet end and the inlet to the MS. In positive mode operation a voltage in the kilo volt range is usually applied to the capillary outlet while the inlet to the MS is grounded. In negative mode operation the capillary outlet will be grounded and a voltage in the kilo volt range will be applied to the inlet of the MS. When operating the MS in positive mode, positively charged ions are drawn from the capillary towards the inlet of the MS. The positively charged ions will withdraw solvent and sample components present in the solvent. Following CRM, single charged sample ions are finally generated. In the negative mode, negative ions are attracted by the inlet of the MS.
16Yamashita, M.; Fenn, J. B. J. Chem. Phys. 1984, 88, 4451. 
One disadvantage when considering coupling of a separation system with an ESI-MS is that the same separation column is used for long periods of time due to the costs of purchasing these columns. This is especially true for packed capillary columns. MEKC comprises a different type of chromatography where a new selector phase is used in every new separation. However, MEKC can not be used directly with an MS since the micelles and surfactants present in the mobile phase will contaminate the MS, increase the noise and lower the ionization efficiency of the sample components leading to detection limit reductions.
Absorption of sample components to the sample handling equipment is a major problem in analytical chemistry. This problem needs to be particularly addressed today as the evolution of the analytical chemistry is directed towards miniaturization, e.g. analysis of a single living cell. According to the discussion above it is of great concern to develop and invent systems and methods that are able to handle, separate and analyze samples in an efficient manner without loss of sample components. The invention described in this application offers a unique solution to these problems.